TY - GEN
T1 - Recent structural and mechanistic insights into endplate acetylcholine receptors
AU - Sine, Steven M.
AU - Gao, Fan
AU - Lee, Won Yong
AU - Mukhtasimova, Nuriya
AU - Wang, Hai Long
AU - Engel, Andrew G.
PY - 2008/6
Y1 - 2008/6
N2 - Voluntary movement mediated by skeletal muscle relies on endplate acetylcholine receptors (AChR) to detect nerve-released ACh and depolarize the muscle fiber. Recent structural and mechanistic studies of the endplate AChR have catalyzed a leap in our understanding of the molecular steps in this chemical-to-electrical transduction process. Studies of acetylcholine binding protein (AChBP) give insight into ACh recognition, the first step in activation of the AChR. An atomic structural model of the Torpedo AChR at a resolution of 0.4 nm, together with single-ion channel recording methods, allow tracing of the link between the agonist binding event and gating of the ion channel, as well as determination of how the channel moves when it opens to allow flow of cations. Structural models of the human AChR enable precise mapping of disease-causing mutations, while studies of the speed with which single AChR channels open and close cast light on pathogenic mechanisms.
AB - Voluntary movement mediated by skeletal muscle relies on endplate acetylcholine receptors (AChR) to detect nerve-released ACh and depolarize the muscle fiber. Recent structural and mechanistic studies of the endplate AChR have catalyzed a leap in our understanding of the molecular steps in this chemical-to-electrical transduction process. Studies of acetylcholine binding protein (AChBP) give insight into ACh recognition, the first step in activation of the AChR. An atomic structural model of the Torpedo AChR at a resolution of 0.4 nm, together with single-ion channel recording methods, allow tracing of the link between the agonist binding event and gating of the ion channel, as well as determination of how the channel moves when it opens to allow flow of cations. Structural models of the human AChR enable precise mapping of disease-causing mutations, while studies of the speed with which single AChR channels open and close cast light on pathogenic mechanisms.
KW - Acetylcholine binding protein
KW - Acetylcholine receptor
KW - Agonist recognition
KW - Binding-gating coupling mechanism
KW - Congenital myasthenic syndrome
UR - http://www.scopus.com/inward/record.url?scp=45249102047&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45249102047&partnerID=8YFLogxK
U2 - 10.1196/annals.1405.041
DO - 10.1196/annals.1405.041
M3 - Conference contribution
C2 - 18567853
AN - SCOPUS:45249102047
SN - 9781573316873
T3 - Annals of the New York Academy of Sciences
SP - 53
EP - 60
BT - Myasthenia Gravis and Related Disorders 11th International Conference
PB - Blackwell Publishing Inc.
ER -